6 research outputs found
Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2
- Author
- Abellán Javier
- Acosta-isaac René
- Aguado Jose María
- Aguilar Carlos
- Aguilera-albesa Sergio
- Ahmadi Sabbagh Abdolah
- Alba Jorge
- Albu Sergiu
- Alcalá-gallardo Karla A. M.
- Alcoba-florez Julia
- Alcolea Batres Sergio
- Algarin-lara Holmes Rafael
- Almadana Virginia
- Almeida Julia
- Almoguera Berta
- Alonso María R.
- Andreu-bernabeu Álvaro
- Antonijoan Maria Rosa
- Arana-arri Eunate
- Aranda Carlos
- Arango Celso
- Araque Carolina
- Araujo Izabel M. T.
- Araujo Nathalia K.
- Arcanjo Ana C.
- Arnaiz Ana
- Arnalich Fernández Francisco
- Arranz María J.
- Arribas López José Ramón
- Artiga Maria-jesús
- Avello-malaver Yubelly
- Ayuso Carmen
- Balagué-dobón Laura
- Baldion Ana María
- Ballina Martín Belén
- Baptista-rosas Raúl C.
- Barranco-díaz Andrea
- Barreda-sánchez María
- Barrera-penagos Viviana
- Belhassen-garcia Moncef
- Bernal Enrique
- Bernal-bello David
- Bezerra Joao F.
- Bezerra Marcos A. C.
- Blanca-lópez Natalia
- Blancas Rafael
- Boix-palop Lucía
- Borobia Alberto
- Bravo Elsa
- Brion María
- Brochado-kith Óscar
- Brugada Ramón
- Bustos Matilde
- Cabello Alfonso
- Calbo Esther
- Calderón Enrique J.
- Camacho Shirley
- Campos Marcela C.
- Carbonell Cristina
- Cardona-huerta Servando
- Carioca Antonio Augusto F.
- Carpio Segura Carlos
- Carracedo Ángel
- Carratto Thássia M. T.
- Carrillo-avila José Antonio
- Carvalho Maria C. C.
- Casasnovas Carlos
- Castaño Carlos F.
- Castaño Luis
- Castelao Jose E.
- Castellano Candalija Aranzazu
- Castillo María A.
- Cañadas Yolanda
- Ceballos Francisco C.
- Chaux Jessica G.
- Chaves-santiago Walter G.
- Chiquillo-gómez Sylena
- Cid-lópez Marco A.
- Cienfuegos-jiménez Óscar
- Conde-vicente Rosa
- Cordero-lorenzana M. Lourdes
- Corella Dolores
- Corrales Almudena
- Corton Marta
- Cortés-sánchez Jose L.
- Costa Tatiana X.
- Cruz Marina S.
- Cruz Raquel
- Cuesta Luisa
- Cunha Gabriela C. R.
- Cáceres Alejandro
- Cáceres-agra Juan J.
- Dalmau David
- Dantas-komatsu Raquel C. S.
- Darnaude M. Teresa
- De Andrés Raimundo
- De Araújo Jéssica N. G.
- De Juan Carmen
- De La Cruz Troca Juan J.
- De La Horra Carmen
- De La Hoz Ana B.
- De Martino-rodríguez Alba
- De Sousa Alves Neri Julianna Lys
- Del Campo-pérez Victor
- Delgado-cuesta Juan
- Diaz De Bustamante Aranzazu
- Dietl Beatriz
- Diz-de Almeida Silvia
- Do Monte Alves Manoella
- Domínguez-garrido Elena
- Dos Santos Katiusse A.
- Duarte Alice L.
- Díaz-caneja Covadonga M.
- Díaz-pérez Anderson
- Echave-sustaeta Jose
- Eiros Rocío
- Enciso-olivera César O.
- Escudero Gabriela
- Esko Tonu
- España Pedro Pablo
- Estigarribia Sanabria Gladys
- Fariñas María Carmen
- Fernandes Marianne R.
- Fernandez-nestosa María J.
- Fernández Martínez Yolanda
- Fernández Ramón
- Fernández Ruth
- Fernández-caballero Lidia
- Fernández-capitán Carmen
- Fernández-cruz Ana
- Fernández-ferrero Silvia
- Fernández-robelo Uxía
- Fernández-rodríguez Amanda
- Fernández-sampedro Marta
- Fernández-villa Tania
- Flores Carlos
- Flores-pérez Patricia
- Friaza Vicente
- Fuenmayor-hernández Lácides
- Fuertes-núñez Marta
- Fumadó Victoria
- Gadea Ignacio
- Gagliardi Lidia
- Gago-domínguez Manuela
- Gallego Natalia
- Galoppo Cristina
- Garcia-garcía Josefina
- García Torrejón María Carmen
- García Inés
- García Leticia
- García Mercedes
- García-cerrada Carlos
- García-de-vicuña Aitor
- García-garcía Irene
- García-ibarbia Carmen
- García-montero Andrés C.
- García-soidán Ana
- García-vázquez Elisa
- Garza-frias Emiliano
- Gentile Angela
- Gil-fournier Belén
- Gonzalez-sagrado Manuel
- Gonzalo-benito Hugo
- González Bernaldo De Quirós Fernán
- González Álvarez Beatriz
- González Juan R.
- González Juan R.
- González-montelongo Rafaela
- González-neira Anna
- González-peñas Javier
- Gorgojo-galindo Oscar
- Guaragna Florencia
- Guegel Genilson P.
- Guillén-guío Beatriz
- Guillén-navarro Encarna
- Guisado-vasco Pablo
- Gutiérrez-bautista Juan F.
- Gutiérrez-castañeda Luz D.
- Gómez Carrera Luis
- Gómez García María
- Gómez Sacristán Ángela
- Gómez-arrue Javier
- Gómez-duque Mario
- Górgolas Miguel
- Heili-frades Sara
- Hernández Estefania
- Hernández-moro Cristina
- Hernández-ortega Luis D.
- Hernández-pérez Guillermo
- Hernández-vaquero Rebeca
- Herranz M. Teresa
- Herrera María
- Herrero María José
- Herrero-gonzález Antonio
- Herráez Belén
- Horcajada Juan P.
- Imaz-ayo Natale
- Intxausti-urrutibeaskoa Maider
- Jacomo Rafael H.
- Jara Rubén
- Jiménez Pilar
- Jiménez Ángel
- Jiménez-alfaro Ignacio
- Jiménez-sousa María A.
- Jordan Iolanda
- Laguna-goya Rocío
- Laorden Daniel
- Lapunzina Pablo
- Lasa-lázaro María
- Lattig María Claudia
- Lauriente Ailen
- Liger Borja Anabel
- Llanos Lucía
- Lopez-garcia Esther
- Lopez-rodriguez Rosario
- Lorente Leonardo
- Lorenzo-salazar José M.
- Lozano José E.
- Lozano-espinosa María
- Luchessi Andre D.
- López De Heredia Miguel
- López De Heredia Miguel
- López-bernús Amparo
- López-granados Eduardo
- López-ruz Miguel A.
- Mahillo Ignacio
- Mancebo Esther
- Mar Carmen
- Marcelo Calvo Cristina
- Marcos Miguel
- Marcos-delgado Alba
- Mariscal-aguilar Pablo
- Martin-fernandez Marta
- Martin-pedraza Laura
- Martinez Amalia
- Martinez-paz Pedro
- Martín María Dolores
- Martín María M.
- Martín Vicente
- Martín-lópez Caridad
- Martín-oterino José-Ángel
- Martín-vicente María
- Martínez Juan José
- Martínez Ricardo
- Martínez Silvia
- Martínez-aquino Eleno
- Martínez-gonzález Óscar
- Martínez-lópez Iciar
- Martínez-nieto Óscar
- Martínez-pérez Ángel
- Martínez-ramas Andrea
- Martínez-reséndez Michel F.
- Martínez-robles Violeta
- Marzal Laura
- Marín-candón Alicia
- Maya Belén Rodríguez
- Mazzeu Juliana F.
- Medeiros Jeane F. P.
- Medeiros Kelliane A.
- Medrano Francisco J.
- Meijome Xose M.
- Mejuto-montero Natalia
- Mendes Ingrid
- Mendoza Charris Humberto
- Merayo Macías Eleuterio
- Mercadillo Fátima
- Mercado-sesma Arieh R.
- Molina Antonio J. J.
- Molina-roldán Elena
- Montoya Juan José
- Moraes Vitor M. S.
- Moreira-escriche Patricia
- Morelos-arnedo Xenia
- Moreno Cuerda Víctor
- Moreno Fernández Alberto
- Moreno Rocío
- Moreno-docón Antonio
- Moreno-escalante Junior
- Morilla Rubén
- Muñoz García Patricia
- Méndez-echevarría Ana
- Mínguez Pablo
- Neira Pablo
- Nevado Julián
- Nieto-gañán Israel
- Nunes Joana F. R.
- Nuñez-torres Rocío
- Obrador-hevia Antònia
- Ocejo-vinyals J. Gonzalo
- Olivar Virginia
- Oliveira Silviene F.
- Olivera María Rubio
- Ondo Lorena
- Orfao Alberto
- Ortega Luis
- Ortega-paino Eva
- Ortiz-flores Fernando
- Ortiz-lópez Rocío
- Oteo José A.
- Pacheco Manuel
- Pacheco-miranda Fredy Javier
- Padilla-conejo Irene
- Panadero-fajardo Sonia
- Parellada Mara
- Pariente-rodríguez Roberto
- Paz-artal Estela
- Peces-barba Germán
- Pedromingo Kus Miguel S.
- Perales Celia
- Perucho Teresa
- Pichardo Lisbeth A.
- Pinho Susana M. T.
- Pinsach-abuin Mel·lina
- Pinzón Luz Adriana
- Pita Guillermo
- Pla-juncà Francesc
- Planas-serra Laura
- Pompa-mera Ericka N.
- Porras-hurtado Gloria L.
- Pujol Aurora
- Pérez Alexandra
- Pérez César
- Pérez María Jazmín
- Pérez Patricia
- Pérez-de-nanclares Gustavo
- Pérez-garcía Felipe
- Pérez-jurado Luis A.
- Pérez-matute Patricia
- Pérez-tomás M. Elena
- Quevedo-chávez María Eugenia
- Quijada Maria Angeles
- Quintela Inés
- Quintela Inés
- Ramiro-león Soraya
- Rascado Sedes Pedro
- Recalde Delia
- Recio-fernández Emma
- Resino Salvador
- Riancho José A.
- Ribeiro Adriana P.
- Rivadeneira-chamorro Carlos S.
- Roa-agudelo Diana
- Robelo Pardo Montserrat
- Rodriguez Marilyn Johanna
- Rodriguez-nicolas Antonio
- Rodriguez-palmero Agustí
- Rodriguez-urrego Paula A.
- Rodríguez-artalejo Fernando
- Rodríguez-ferrer Marena
- Rodríguez-gallego Carlos
- Rodríguez-garcía José A.
- Rodríguez-hernández María A.
- Rodríguez-novoa German Ezequiel
- Rodríguez-ruiz Emilio
- Rojas-martinez Augusto
- Rojo Federico
- Romero-coronado Andrea
- Rondón-garcía Filomeno
- Rosa Lidia S.
- Rosales-castillo Antonio
- Rubio Cladelis
- Ruiz Montserrat
- Ruiz-cabello Francisco
- Ruiz-casares Eva
- Ruiz-cubillan Juan J.
- Ruiz-hornillos Javier
- Ryan Pablo
- Salamanca Hector D.
- Salazar-garcía Lorena
- Salgueiro-origlia Giorgina Gabriela
- Sancho-sainz Cristina
- Sande Esther
- Sangil Anna
- Santos Arnoldo
- Santos Ney P. C.
- Schlüter Agatha
- Scourge Cohort Group
- Segovia Sonia
- Serra-llovich Alex
- Sevil-puras Fernando
- Sevilla-porras Marta
- Sicolo Miguel A.
- Silbiger Vivian N.
- Silva Fabiola T. C.
- Silva Gabriela V.
- Silva Nayara S.
- Silván-fuentes Cristina
- Solé-violán Jordi
- Soria José Manuel
- Sorlí Jose V.
- Sousa Renata R.
- Souto Juan Carlos
- Souza Karla S. C.
- Souza Vanessa S.
- Sprockel John J.
- Suárez-rama José Javier
- Suárez-zamora David A.
- Sánchez López Antonio J.
- Sánchez Pedro-luis
- Sánchez-carpintero Abad María
- Sánchez-pablo Clara
- Sánchez-pernaute Olga
- Sánchez-prados María Concepción
- Sánchez-real Javier
- Sánchez-redondo Jorge
- Taboada-fraga Xiana
- Tamayo Eduardo
- Tamayo-velasco Alvaro
- Taracido-fernández Juan Carlos
- Tavares Nathali A. C.
- Tellería Carlos
- Tenorio-castaño Jair Antonio
- Teper Alejandro
- Torres-gutiérrez Ronald P.
- Torres-macho Juan
- Torres-tobar Lilian
- Troya Jesús
- Urioste Miguel
- Valencia-ramos Juan
- Valido Agustín
- Vargas-gallo Juan Pablo
- Varón Belén
- Vasconcelos Romero H. T.
- Vega Tomas
- Velasco-quirce Santiago
- Vidán-estévez Julia
- Vieitez-santiago Miriam
- Vilches Carlos
- Villalobos Lavinia
- Villar Felipe
- Villar-garcia Judit
- Villaverde Cristina
- Villoslada-blanco Pablo
- Virseda-berdices Ana
- Vélez-santamaría Valentina
- Víctor Virginia
- Yáñez Zuleima
- Zapatero-gaviria Antonio
- Zarate Ruth
- Zazo Sandra
- Álvarez Nuria
- Álvarez-benítez Yady
- Álvarez-navia Felipe
- Álvarez-sala Walther Rodolfo
- Íñigo-campos Antonio
- Íñiguez María
- Publication venue
- Springer Science and Business Media LLC
- Publication date
- 08/05/2024
- Field of study
The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality
Variabilidad entre patólogos en el diagnóstico histológico de las enfermedades intersticiales difusas del pulmón
- Author
- Publication venue
- 'Elsevier BV'
- Publication date
- 01/01/2005
- Field of study
Objetivo: Las enfermedades pulmonares intersticiales difusas (EPID) son un conjunto de enfermedades que afecta al espacio alveolointersticial, con manifestaciones clínicas, radiológicas y funcionales muy similares, por lo que en muchos casos el estudio de la biopsia pulmonar será fundamental para el diagnóstico, pronóstico y tratamiento. Hemos querido ver si hay o no concordancia histopatológica diagnóstica, entre diferentes grupos de patólogos, en la valoración de estas enfermedades. Material y métodos: Se han estudiado las biopsias de 33 pacientes afectados de EPID no infecciosa ni tumoral, las cuales han sido valoradas por 2 grupos de patólogos: uno con especial interés por este tipo de enfermedades, y otro grupo no dedicado especialmente a esta enfermedad. Resultados: Al confrontar posteriormente los resultados, observamos en los informes histológicos una discordancia en el diagnóstico de 10 de los 33 casos estudiados (30,3%), 9 de ellos en el grupo de las 22 neumonías intersticiales idiopáticas (40,9%) y un caso en el grupo de las 3 EPID de causas conocidas o asociadas. Sin embargo, no encontramos ninguna discrepancia en el grupo de EPID primarias o asociadas a otros procesos no bien conocidos. Conclusiones: Creemos que las neumonías intersticiales idiopáticas son el grupo de EPID que más problemas de diagnóstico histológico pueden plantear al patólogo. Por tanto, es fundamental una especial dedicación por parte de estos profesionales y de los distintos especialistas que están relacionados con el estudio de las EPID
Variabilidad entre patólogos en el diagnóstico histológico de las enfermedades intersticiales difusas del pulmón
- Author
- Publication venue
- 'Elsevier BV'
- Publication date
- Field of study
Thioredoxin Reductase as a Novel and Efficient Plasma Biomarker for the Detection of Non-Small Cell Lung Cancer: a Large-scale, Multicenter study
- Author
- A Holmgren
- A Mollbrink
- A Soderberg
- B Sahaf
- C Dong
- C Jakupoglu
- C Li
- D Moro
- D Mustacich
- DT Lincoln
- E Sulu
- EL Leung
- ES Arner
- F Bray
- F Li
- F Olesen
- G Chen
- G Powis
- GL Perkins
- GP Currie
- H Nakamura
- J Fang
- L Wang
- LA Torre
- M Berggren
- M Conrad
- M Grunnet
- M Luthman
- M Zhou
- MH Gail
- MH Yoo
- N Kilic
- N Sun
- National Lung Screening Trial Research T
- O Arrieta
- P Brocken
- PB Cassidy
- R Salgia
- RH Christenson
- S Cedres
- S Ma
- S Ramalingam
- SH Landis
- SP Hammar
- TW Fan
- V Almadana Pacheco
- W Zhang
- WC Nugent
- WJ Jusko
- Y Soini
- YS Bahn
- YS Yang
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- Field of study
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- Campbell A
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- Campbell H
- Campbell R
- Campbell S
- Campos MC
- Campos S
- Camsooksai J
- Candalija AC
- Candon AM
- Capitán CF
- Capozzi L
- Capps N
- Carbonell C
- Cardona-Huerta S
- Cardwell A
- Carioca AAF
- Carmody M
- Carmody S
- Carnahan M
- Carpintero MS
- Carracedo A
- Carracedo A
- Carratto TMT
- Carrera LG
- Carrillo-Avila JA
- Carson G
- Cart C
- Carter A
- Carter D
- Carter E
- Carter J
- Carter M
- Carter S
- Cartlidge D
- Carungcong J
- Carvalho MCC
- Casasnovas C
- Casey M
- Castano L
- Castaño CF
- Castaño JAT
- Castelao JE
- Castillo MA
- Caswell M
- Caterson J
- Cathcart S
- Catlow L
- Cavazza A
- Cave A
- Cawley K
- Cawley K
- Cawthron K
- Cañadas Y
- Ceballos FC
- Cha M
- Chablani M
- Chadwick R
- Chan R
- Chand M
- Chandler B
- Chandna H
- Chapman S
- Charles B
- Charlesworth R
- Charnock R
- Charris HM
- Chaux JG
- Chaves-Santiago WG
- Chechi K
- Cheema Y
- Chen J
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- Chesters K
- Chetam L
- Cheyne C
- Chikowore P
- Childs D
- Chiquillo-Gómez S
- Chisholm C
- Choudhr O
- Choudhury Y
- Chukkambotla S
- Chávez MEQ
- Cid-Lopez MA
- Cienfuegos-Jimenez O
- Cinquina Z
- Clamp S
- Clapham M
- Clarey E
- Claridge H
- Clark A
- Clark A
- Clark M
- Clark M
- Clark R
- Clark R
- Clark S
- Clark S
- Clark V
- Clarke N
- Clarkson M
- Clayton S
- Clement I
- Clements S
- Clohisey S
- Coates C
- Cochrane P
- Cockerill H
- Cockrell M
- Coe R
- Coetzee S
- Coghlan P
- Cohrane C
- Coker D
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- Colley N
- Collier D
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- Collins A
- Collins C
- Collins E
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- Collins R
- Collins V
- Collis M
- Combes E
- Conde-Vicente R
- Conejo IP
- Connell J
- Connolly K
- Connor M
- Convery K
- Conyngham J-A
- Cooke GS
- Cookson R
- Cooper J
- Cooper L
- Cooper L
- Corcoran E
- Corcoran K
- Cordero-Lorenzana ML
- Corella D
- Corin C
- Cornell S
- Cornell T
- Corner A
- Corral MA
- Corrales A
- Cortes-Sanchez JL
- Corton M
- Cosgrove D
- Cosier T
- Costa TX
- Cother N
- Coton Z
- Cottam L-J
- Cottle J
- Coulding M
- Coutts A
- Coventry T
- Covernton P
- Cowley A
- Cowley N
- Cowton A
- Cox A
- Coyle J
- Craig H
- Craig J
- Crawley R
- Creagh-Brown B
- Crew A
- Crickmore V
- Cristiano D
- Croft M
- Crowe R
- Crowley M
- Cruz C
- Cruz MS
- Cruz R
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- Csabi P
- Cuerda VM
- Cuesta L
- Cullum L
- Cunha GCR
- Cunningham A
- Cunningham M
- Cupitt J
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- Da Gloria EF
- Da Rocha J
- da Silva Filipe A
- da Silva GV
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- Dagutao Z
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- Dalton C
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- Daly Z
- Dalziel J
- DAmato F
- Dance A
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- Daniel E
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- Darnaude MT
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- Dawson A
- Dawson D
- Day A
- Day N
- de Andrés R
- de Araújo JNG
- De Beger S
- de Bustamante AD
- de Gordoa LO-R
- de Heredia ML
- de Juan C
- De la Cruz Troca J
- de la Horra C
- de la Hoz AB
- De Martino-Rodríguez A
- de Neef M
- De Queiroz JG
- de Quirós FGB
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- de Sousa Alves Neri JL
- Deacon B
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- DeAth Y
- Debreceni G
- Deery J
- del Campo-Pérez V
- Dela Rosa A
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- Dexter C
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- Dickson H
- Dietl B
- Digby B
- Digby S
- Ding L
- Diz-de Almeida S
- Djeugam B
- Doble P
- Dobson E
- Docherty AB
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- Domínguez-Garrido E
- Donaldson A
- Donaldson D
- Donegan C
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- Doonan R
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- dos Santos KA
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- Durrant G
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- Earl V
- Eastgate C
- Easthope A
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- Escudero G
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- España PP
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- Fernandez-Nestosa MJ
- Fernandez-Roman J
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- Fernández-Robelo U
- Fernández-Rodríguez A
- Fernández-Sampedro M
- Fernández-Sánchez R
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- Ferrero SF
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- García FR
- García I
- García L
- García M
- García MG
- García PM
- García-de-Vicuña A
- García-García I
- García-Ibarbia C
- García-Montero AC
- García-Soidán A
- García-Vázquez E
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- Íñiguez M
- Publication venue
- Springer Nature
- Publication date
- 17/05/2023
- Field of study
Data availability: Downloadable summary data are available through the GenOMICC data site (https://genomicc.org/data). Summary statistics are available, but without the 23andMe summary statistics, except for the 10,000 most significant hits, for which full summary statistics are available. The full GWAS summary statistics for the 23andMe discovery dataset will be made available through 23andMe to qualified researchers under an agreement with 23andMe that protects the privacy of the 23andMe participants. For further information and to apply for access to the data, see the 23andMe website (https://research.23andMe.com/dataset-access/). All individual-level genotype and whole-genome sequencing data (for both academic and commercial uses) can be accessed through the UKRI/HDR UK Outbreak Data Analysis Platform (https://odap.ac.uk). A restricted dataset for a subset of GenOMICC participants is also available through the Genomics England data service. Monocyte RNA-seq data are available under the title ‘Monocyte gene expression data’ within the Oxford University Research Archives (https://doi.org/10.5287/ora-ko7q2nq66). Sequencing data will be made freely available to organizations and researchers to conduct research in accordance with the UK Policy Framework for Health and Social Care Research through a data access agreement. Sequencing data have been deposited at the European Genome–Phenome Archive (EGA), which is hosted by the EBI and the CRG, under accession number EGAS00001007111.Extended data figures and tables are available online at https://www.nature.com/articles/s41586-023-06034-3#Sec21 .Supplementary information is available online at https://www.nature.com/articles/s41586-023-06034-3#Sec22 .Code availability:
Code to calculate the imputation of P values on the basis of SNPs in linkage disequilibrium is available at GitHub (https://github.com/baillielab/GenOMICC_GWAS).Acknowledgements: We thank the members of the Banco Nacional de ADN and the GRA@CE cohort group; and the research participants and employees of 23andMe for making this work possible. A full list of contributors who have provided data that were collated in the HGI project, including previous iterations, is available online (https://www.covid19hg.org/acknowledgements).Change history: 11 July 2023: A Correction to this paper has been published at: https://doi.org/10.1038/s41586-023-06383-z. -- In the version of this article initially published, the name of Ana Margarita Baldión-Elorza, of the SCOURGE Consortium, appeared incorrectly (as Ana María Baldion) and has now been amended in the HTML and PDF versions of the article.Copyright © The Author(s) 2023, Critical illness in COVID-19 is an extreme and clinically homogeneous disease phenotype that we have previously shown1 to be highly efficient for discovery of genetic associations2. Despite the advanced stage of illness at presentation, we have shown that host genetics in patients who are critically ill with COVID-19 can identify immunomodulatory therapies with strong beneficial effects in this group3. Here we analyse 24,202 cases of COVID-19 with critical illness comprising a combination of microarray genotype and whole-genome sequencing data from cases of critical illness in the international GenOMICC (11,440 cases) study, combined with other studies recruiting hospitalized patients with a strong focus on severe and critical disease: ISARIC4C (676 cases) and the SCOURGE consortium (5,934 cases). To put these results in the context of existing work, we conduct a meta-analysis of the new GenOMICC genome-wide association study (GWAS) results with previously published data. We find 49 genome-wide significant associations, of which 16 have not been reported previously. To investigate the therapeutic implications of these findings, we infer the structural consequences of protein-coding variants, and combine our GWAS results with gene expression data using a monocyte transcriptome-wide association study (TWAS) model, as well as gene and protein expression using Mendelian randomization. We identify potentially druggable targets in multiple systems, including inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).GenOMICC was funded by Sepsis Research (the Fiona Elizabeth Agnew Trust), the Intensive Care Society, a Wellcome Trust Senior Research Fellowship (to J.K.B., 223164/Z/21/Z), the Department of Health and Social Care (DHSC), Illumina, LifeArc, the Medical Research Council, UKRI, a BBSRC Institute Program Support Grant to the Roslin Institute (BBS/E/D/20002172, BBS/E/D/10002070 and BBS/E/D/30002275) and UKRI grants MC_PC_20004, MC_PC_19025, MC_PC_1905 and MRNO2995X/1. A.D.B. acknowledges funding from the Wellcome PhD training fellowship for clinicians (204979/Z/16/Z), the Edinburgh Clinical Academic Track (ECAT) programme. This research is supported in part by the Data and Connectivity National Core Study, led by Health Data Research UK in partnership with the Office for National Statistics and funded by UK Research and Innovation (grant MC_PC_20029). Laboratory work was funded by a Wellcome Intermediate Clinical Fellowship to B.F. (201488/Z/16/Z). We acknowledge the staff at NHS Digital, Public Health England and the Intensive Care National Audit and Research Centre who provided clinical data on the participants; and the National Institute for Healthcare Research Clinical Research Network (NIHR CRN) and the Chief Scientist’s Office (Scotland), who facilitate recruitment into research studies in NHS hospitals, and to the global ISARIC and InFACT consortia. GenOMICC genotype controls were obtained using UK Biobank Resource under project 788 funded by Roslin Institute Strategic Programme Grants from the BBSRC (BBS/E/D/10002070 and BBS/E/D/30002275) and Health Data Research UK (HDR-9004 and HDR-9003). UK Biobank data were used in the GSMR analyses presented here under project 66982. The UK Biobank was established by the Wellcome Trust medical charity, Medical Research Council, Department of Health, Scottish Government and the Northwest Regional Development Agency. It has also had funding from the Welsh Assembly Government, British Heart Foundation and Diabetes UK. The work of L.K. was supported by an RCUK Innovation Fellowship from the National Productivity Investment Fund (MR/R026408/1). J.Y. is supported by the Westlake Education Foundation. SCOURGE is funded by the Instituto de Salud Carlos III (COV20_00622 to A.C., PI20/00876 to C.F.), European Union (ERDF) ‘A way of making Europe’, Fundación Amancio Ortega, Banco de Santander (to A.C.), Cabildo Insular de Tenerife (CGIEU0000219140 ‘Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19’ to C.F.) and Fundación Canaria Instituto de Investigación Sanitaria de Canarias (PIFIISC20/57 to C.F.). We also acknowledge the contribution of the Centro National de Genotipado (CEGEN) and Centro de Supercomputación de Galicia (CESGA) for funding this project by providing supercomputing infrastructures. A.D.L. is a recipient of fellowships from the National Council for Scientific and Technological Development (CNPq)-Brazil (309173/2019-1 and 201527/2020-0)
A second update on mapping the human genetic architecture of COVID-19
- Author
- Abd Elghafar MS
- Abdel-Aziz M
- Abdelrazik M
- Abdullah MS
- Abe R
- Abe S
- Abel L
- Abel L
- Abernathy C
- Abraham R
- Abraheem A
- Abu Alragheb BO
- Abulail JA
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- Pathak GA
- Pathan N
- Patience D
- Patil A
- Patin E
- Pattison N
- Paul P
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- Pawley C
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- Pellegrin I
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- Polikowsky HG
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- Pompa-Mera EN
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- Postovalova E
- Pothecary C
- Potla D
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- Prokić I
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- Sainsbury H
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- Sekikawa Y
- Sell C
- Sellick K
- Selvanayagam S
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- Senaratne D
- Senner F
- Sequeros CB
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- Shamah-Levy T
- Shankar-Hari M
- Shanmugasundaram P
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- Shen X
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- Shepperson A
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- Shivanathan I
- Shokkar R
- Shoko T
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- Shoremekun A
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- Solier A
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- Solligård E
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- Solomonson M
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- Sonobe K
- Soria JM
- Soriano A
- Souto JC
- Speight A
- Speirs S
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- Spinner CD
- Spivey M
- Springle P
- Sra S
- Sri-Chandana C
- Srikaran S
- St-Cyr J
- Stacey A
- Stagg C
- Stammers K
- Stapleton L
- Stark KJ
- Stead R
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- Sugiyama M
- Sukha A
- Sukhatme MG
- Sukumaran A
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- Szakmany T
- Szentpéteri JL
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- Takahashi M
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- Takeda Y
- Takeuchi M
- Taki R
- Tamayo E
- Tamayo-Velasco A
- Tampsett R
- Tanaka A
- Tanaka H
- Tanate A
- Tanck A
- Taneski F
- Tani M
- Tanigawa Y
- Tanino Y
- Taniyama D
- Tanudjaja F
- Taracido-Fernandez JC
- Tardif N
- Tariq A
- Tateishi T
- Tateno H
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- Tauekelova A
- Tauro S
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- Taylor B
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- Tetla D
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- Tibke C
- Tiembe N
- Tierney C
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- Timens W
- Timlick E
- Timpson NJ
- Ting L
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- Tivenan H
- Toapanta D
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- Tselios C
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- Turney S
- Turtle L
- Turvey SE
- Tusié-Luna T
- Tutt G
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- Twiss S
- Tyl D
- Tyler A
- Tzoulaki I
- Téllez L
- Uchimura Y
- Ueda S
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- Uitterlinden AG
- Ullum H
- Umeda A
- Upadhyay KJ
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- Usher M
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- Uwamino Y
- Vadgama N
- Vadla MS
- Vaida M
- Valdeavella K
- Valdés PA
- Valencia-Ramos J
- Valenti L
- Valenzuela-Jorquera H
- Vallerga CL
- Valsecchi MG
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- Van Heel DA
- Van Heel DA
- Van Koutrick L
- Vandernoot I
- Varghese M
- Vasilevska-Ristovska J
- Vassell K
- Vedage D
- Veerapen K
- Vega J
- Vehreschild MJGT
- Velasco DG
- Velázquez-Cruz R
- Venkatesh H
- Verdugo RA
- Verdugo RA
- Vergasova E
- Verlander M
- Vertue M
- Verula J
- Vigueras-Hernández A
- Vigurs C
- Villa A
- Villalonga JM
- Vincent R
- Virgilio E
- Virginia M-RA
- Vitart V
- Vizcaychipi M
- Vlasschaert C
- Vochin A
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- Von Hohenstaufen Puoti KA
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- Vuylsteke A
- Várnai R
- Vázquez-Pérez JA
- Wacker EM
- Wackett T
- Wadams B
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- Waite AAC
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- Wakahara K
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- Wakinshaw F
- Waldron J
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- Wang X
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- Washington NL
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- Watanabe K
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- Wells C
- Welters I
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- Wendtner CM
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- Weston H
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- Wolford BN
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- Wulandari R
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- Wyllie DH
- Wynter I
- Xavier K
- Xue X
- Yagi K
- Yamada M
- Yamada Y
- Yamagata K
- Yamasaki M
- Yang J
- Yaspan B
- Yassen AM
- Yasui Y
- Yates B
- Yatomi M
- Ye C
- Yermakovich D
- Yeung RSM
- Yi X
- Yonekawa A
- Yoo S
- Yoon K
- Yoshida K
- Yoshida S
- Yoshida S
- Yoshida T
- Yoshihara T
- Yoshiya K
- Yoshiyama T
- Young M
- Yue F
- Yun N
- Yáñez CE
- Yáñez Z
- Zainulabid UA
- Zainy T
- Zak A
- Zaki A
- Zamikula J
- Zamudio IPM
- Zanella A
- Zapata-Contreras D
- Zapatamartinez M
- Zarate R
- Zarei N
- Zavaleta DAF
- Zawadzki P
- Zawati MH
- Zborowski AC
- Zeberg H
- Zechner M
- Zhang Q
- Zhao X
- Zheng C
- Zheng T
- Zhlawi HJ
- Zhlawi MWJ
- Zholdybayeva E
- Zhou W
- Zhu W
- Zitter L
- Zoller H
- Zongo O
- Zorloni C
- Zuñiga-Pacheco P
- Zárate RN
- Zúñiga-Ramos J
- Álvarez BG
- Ávila-Arcos MA
- Ávila-Arcos MC
- Özer O
- Überla K
- Þorsteinsdóttir U
- Publication venue
- Nature Research
- Publication date
- 21/06/2023
- Field of study